Glucagon-like peptide 1(GLP-1) in biology and pathology

Diabetes/Metabolism Research and Reviews

Volumn 21, Issue 2, 2005, Pages 91-117

  Meier, Juris J ^a   Nauck, Michael A ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b DIABETESZENTRUM BAD LAUTERBERG   (Germany)

Author keywords

GLP 1; Glucagon like peptide 1; Incretin hormones; Insulin secretion; Type 2 diabetes

Indexed keywords

6 [[2 [[2 (2 CYANO 1 PYRROLIDINYL) 2 OXOETHYL]AMINO]ETHYL]AMINO]NICOTINONITRILE; ANTIDIABETIC AGENT; BENZOIC ACID DERIVATIVE; C PEPTIDE; CJC 1131; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GASTRIC INHIBITORY POLYPEPTIDE; GLICENTIN; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; GLUCAGON LIKE PEPTIDE 2; GLUCOSE; HORMONE; INCRETIN; INSULIN; ISOPHANE INSULIN; LIRAGLUTIDE; LY 307161; PLACEBO; PREPROGLUCAGON; PYRROLIDINE DERIVATIVE; SULFONYLUREA; UNCLASSIFIED DRUG;

ANTIBODY PRODUCTION; ASPIRATION; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL TRIAL; DRUG HALF LIFE; DRUG MECHANISM; DRUG STRUCTURE; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; IMMUNOPATHOLOGY; INJECTION SITE REACTION; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN PROCESSING; REFLUX ESOPHAGITIS; REVIEW; SIDE EFFECT; STOMACH EMPTYING; STRESS; VOMITING; WEIGHT REDUCTION;

ANIMALS; BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON; GLUCAGON-LIKE PEPTIDE 1; HUMANS; PEPTIDE FRAGMENTS; PROTEIN PRECURSORS;

EID: 16344374278     PISSN: 15207552     EISSN: None     Source Type: Journal    
DOI: 10.1002/dmrr.538     Document Type: Review

References (320)

1. Moore B, Edie ES, Abram JH. On the treatment of diabetes mellitus by acid extract of duodenal mucous membrane. Biochem J 1906; 1: 28-38.
2. Zunz E, La Barre J. Contributions a l'étude des variations physiologiques de la sérétion interne du pancréas: relations entre les sérétions externe et interne di pancréas. Arch Int Physiol 1929; 31: 20-44.
3. Berson SA, Yallow RS. Immunoassay of plasma insulin. Ciba Coll Endocrinology 1962; 41: 182-201.
4. Elrick H, Stimmler L, Hlad CJ, Arai Y. Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab 1964; 24: 1076-1082.
5. McIntyre N, Holdsworth CD, Turner DS. Intestinal factors in the control of insulin secretion. J Clin Endocrinol 1965; 25: 1317-1324.
6. Creutzfeldt W. The incretin concept today. Diabetologia 1979; 16: 75-85.
7. Creutzfeldt W, Nauck M. Gut hormones and diabetes mellitus. Diabetes/Metab Rev 1992; 8: 149-177.
8. Nauck MA, Homberger E, Siegel EG, et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 1986; 63: 492-498.
9. Shuster LT, Go VLW, Rizza RA, O'Brien PC, Service FJ. Incretin effect due to increased secretion and decreased clearance of insulin in normal humans. Diabetes 1988; 37: 200-203.
10. Tillil H, Shapiro ET, Miller A, et al. Dose-dependent effects of oral and intravenous glucose on insulin secretion and clearance in normal humans. Am J Physiol (Endocrinol Metab) 1988; 254: E349-E357.
11. Brown JC, Mutt V, Pederson RA. Further purification of a polypeptide demonstrating enterogastrone activity. J Physiol 1970; 209: 57-64.
12. Brown JC, Dryburgh JR. A gastric inhibitory polypeptide II. The complete amino acid sequence. Can J Biochem 1971; 49: 867-872.
13. Brown JC. A gastric inhibitory polypeptide. I. The amino acid composition and the tryptic peptides. Can J Biochem 1971; 49: 255-261.
14. Dupré J, Ross SA, Watson D, Brown JC. Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab 1973; 37: 826-828.
15. Pederson RA, Brown JC. The insulinotropic action of gastric inhibitory polypeptide in the perfused rat pancreas. Endocrinology 1976; 99: 780-785.
16. Pederson RA, Brown JC. Interaction of gastric inhibitory polypeptide, glucose, and arginine on insulin and glucagon secreton from the perfused rat pancreas. Endocrinol 1978; 103: 610-615.
17. Brown JC, Pederson RA. GI hormones and insulin secretion. Endocrinology. Proc Vth Int Cong Endocrinol 1976; 2: 568-570.
18. Bell GI, Santerre RF, Mullenbach GT. Hamster preproglucagon gene contains the sequence of glucagon and two related peptides. Nature 1983; 302: 716-718.
19. Bell GI. The glucagon super family: precursor structure and gene organization. Peptides 1986; 7(Suppl. 1): 27-36.
20. Holst JJ. Evidence that enteroglucagon (II) is identical with the C-terminal sequence (residues 33-69) of glicentin. Biochem J 1982; 207: 381-388.
21. Ørskov C, Knuhtsen S, Baldissera FG, Poulsen SS, Nielsen OV, Holst JJ. Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas. Endocrinology 1986; 119: 1467-1475.
22. Ørskov C, Holst JJ. Radio-immunoassays for glucagon-like peptides 1 and 2 (GLP-1 and GLP-2). Scand J Clin Lab Invest 1987; 47: 165-174.
23. Ørskov C, Holst JJ, Seier-Poulsen S, Kirkegaard P. Pancreatic and intestinal processing of proglucagon in man. Diabetologia 1987; 30: 874-881.
24. Holst JJ, Ørskov C, Vagn-Nielsen O, Schwartz TW. Truncated glucagon-like peptide 1, an insulin-releasing hormone from the distal gut. FEBS Letters 1987; 211: 169-174.
25. Holst JJ. Degradation of pancreatic peptides: glucagon. In Degradation of Bioactive Substances, Physiology and Pathophysiology, Henriksen JH (ed). CRC press, Inc.: Boca Raton, 1991; 167-180.
26. Schmidt WE, Siegel EG, Creutzfeldt W. Glucagon-like peptide 1 but not glucagon-like peptide 2 stimulates insulin release from isolated rat pancreatic islets. Diabetologia 28: 704-707, 1985.
27. Mojsov S, Weir GC, Habener JF. Insulinotropin: glucagon-like peptide I (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas. J Clin Invest 1987; 79: 616-619.
28. Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci USA 1987; 84: 3434-3438.
29. Bailey CJ, Flatt PR. Glucagon-like peptide-1 and the entero-insular axis in obese hyperglycaemic (ob/ob) mice. Life Sci 1987; 40: 521-525.
30. Kreymann B, Williams G, Ghatei MA, Bloom SR. Glucagon-like peptide-1 [7-36]: a physiological incretin in man. Lancet 1987; 2: 1300-1304.
31. Eissele R, Göke R, Willemer S, et al. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 1992; 22: 283-291.
32. Kauth T, Metz J. Immunohistochemical localization of glucagon-like peptide 1. Use of poly- and monoclonal antibodies. Histochemistry 1987; 86: 509-515.
33. Buffa B, Polak JM, Pearse AGE, Solcia E, Grimelius L, Capella C. Identification of the intestinal cell storing gastric inhibitory polypeptide. Histochemistry 1975; 43: 249-255.
34. Buchan AMJ, Polak JM, Capella C, Solcia E, Pearse AGE. Electron immunocytochemical evidence of the K cell localisation of gastric inhibitory polypeptide (GIP) in man. Histochemistry 1978; 56: 37-44.
35. Mortensen K, Petersen LL, Holst JJ, Ørskov C. GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine. Regul Pept 2003; 114: 189-196.
36. El-Ouaghlidi A, Meier JJ, Gabrys B, et al. Unchanged, but correlated secretion of the incretin hormones GIP and GLP-1 after oral glucose in first degree relatives of type 2 diabetic patients and healthy subjects (abstract). Diabetologia 2002; 45(Suppl. 1)): A674.
37. Nauck MA, Bartels E, Ørskov C, Ebert R, Creutzfeldt W. Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near-physiological insulinotropic hormone and glucose concentrations. J Clin Endocrinol Metab 1993; 76: 912-917.
38. Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 1995; 80: 952-957.
39. Herrmann C, Göke R, Richter G, Fehmann HC, Arnold R, Göke B. Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion 1995; 56: 117-126.
40. Kong MF, Chapman I, Goble E, et al. Effects of oral fructose and glucose on plasma GLP-1 and appetite in normal subjects. Peptides 1999; 20: 545-551.
41. Feinle C, Chapman IM, Wishart J, Horowitz M. Plasma glucagon-like peptide 1 (GLP-1) responses to duodenal fat and glucose infusions in lean and obese men. Peptides 2002; 23: 1491-1495.
42. Beysen C, Karpe F, Fielding BA, Clark A, Levy JC, Frayn KN. Interaction between specific fatty acids, GLP-1 and insulin secretion in humans. Diabetologia 2002; 45: 1533-1541.
43. Feinle C, O'Donovan D, Doran S, et al. Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans. Am J Physiol Gastrointest Liver Physiol 2003; 284: G798-G807.
44. Pilichiewicz A, O'Donovan D, Feinle C, et al. Effect of lipase inhibition on gastric emptying of, and the glycemic and incretin responses to, an oil/aqueous drink in type 2 diabetes mellitus. J Clin Endocrinol Metab 2003; 88: 3829-3834.
45. Miholic J, Ørskov C, Holst JJ, Kotzerke J, Meyer HJ. Emptying of the gastric substitute, glucagon-like peptide-1 (GLP-1), and reactive hypoglycemia after total gastrectomy. Dig Dis Sci 1991; 36: 1361-1370.
46. Miholic J, Ørskov C, Holst JJ, Kotzerke J, Pichlmayr R. Postprandial release of glucagon-like peptide-1, pancreatic glucagon, and insulin after esophageal resection. Digestion 1993; 54: 73-78.
47. Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 2001; 50: 609-613.
48. Plaisancie P, Bernard C, Chayvialle JA, Cuber JC. Regulation of glucagon-like peptide-1-(7-36) amide secretion by intestinal neurotransmitters and hormones in the isolated vascularly perfused rat colon. Endocrinology 1994; 135: 2398-2403.
49. Herrmann- Rinke C, Vöge A, Hess M, Göke B. Regulation of glucagon-like peptide-1 secretion from rat ileum by neurotransmitters and peptides. J Endocrinol 1995; 147: 25-31.
50. Schirra J, Katschinski M, Weidmann C, et al. Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest 1996; 97: 92-103.
51. Roberge JN, Brubaker PL. Regulation of intestinal proglucagon-derived peptide secretion by glucose-dependent insulinotropic peptide in a novel enteroendocrine loop. Endocrinology 1993; 133 233-240.
52. Nauck MA, Heimesaat MM, Ørskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 1993; 91 301-307.
53. Fieseler P, Bridenbaugh S, Nustede R, et al. Physiological augmentation of amino acid-induced insulin secretion by GIP and GLP-I but not by CCK-8. Am J Physiol 1995; 268: E949-E955.
54. Anini Y, Hansotia T, Brubaker PL. Muscarinic receptors control postprandial release of glucagon-like peptide-1: in vivo and in vitro studies in rats. Endocrinology 2002; 143: 2420-2426.
55. Anini Y, Brubaker PL. Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells. Endocrinology 2003; 144: 3244-3250.
56. Ranganath LR, Beety LM, Morgan LM, Wright JW, Howland R, Marks V. Attenuated GLP-1 secretion in obesity: cause or consequence? Gut 1996; 38: 916-919.
57. Turton MD, D O'Shea, Gunn I, Beak SA, et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996; 379: 69-72.
58. Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide-1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998; 101: 515-520.
59. Mentlein R, Gallwitz B, Schmidt WE. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1 (7-36) amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 1993; 214: 829-835.
60. Mentlein R. Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides. Regul Pept 1999; 85: 9-24.
61. Kieffer TJ, McIntosh CH, Pederson RA. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 1995; 136: 3585-3596.
62. 2-terminus in type 2-diabetic patients and in healthy subjects. Diabetes 1995; 44: 1126-1131.
63. Montrose Rafizadeh C, Yang H, Rodgers BD, Beday A, Pritchette LA, Eng J. High potency antagonists of the pancreatic glucagon-like peptide-1 receptor. J Biol Chem 1997; 272: 21201-21206.
64. Wettergren A, Wojdemann M, Holst JJ. The inhibitory effect of glucagon-like peptide-1 (7-36) amide on antral motility is antagonized by its N-terminally truncated primary metabolite GLP-1 (9-36) amide. Peptides 1998; 19: 877-882.
65. Grandt D, Sieburg B, Sievert J, et al. Is GLP-1 (9-36) amide an endogenous antagonist at GLP-1 receptors? (abstract). Digestion 1994; 55: 302.
66. 2 on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans. J Clin Endocrinol Metab 2003; 88: 1772-1779.
67. (a) Deacon CF, Pridal L, Klarskov L, Olesen M, Holst JJ. Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig. Am J Physiol (Endocrinol Metab) 1996; 271: E458-E464.
68. (b) Meier JJ, Nauck MA, Kranz D, et al. Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes 2004; 53: 654-662.
69. Lojda Z. Studies on dipeptidyl(amino)peptidase IV (glycyl-proline-naphthylamidase). II. blood vessels. Histochemistry 1979; 59: 153-166.
70. Ruiz Grande C, Pintado J, Alarcon C, Castilla C, Valverde I, Lopez Novoa JM. Renal catabolism of human glucagon-like peptides 1 and 2. Can J Physiol Pharmacol 1990; 68: 1568-1573.
71. Ruiz Grande C, Alarcon C, Merida E, Valverde I. Lipolytic action of glucagon-like peptides in isolated rat adipocytes. Peptides 1992; 13: 13-16.
72. Sirinek KR, O'Dorisio TM, Gaskill HV, Levine BA. Chronic renal failure: effect of hemodialysis on gastrointestinal hormones. Am J Surg 1984; 148: 732-735.
73. Ørskov C, Andreasen J, Holst JJ. All products of proglucagon are elevated in plasma of uremic patients. J Clin Endocrinol Metab 1992; 74: 379-384.
74. Kieffer TJ, Habener JF. The glucagon-like peptides. Endocr Rev 1999; 20: 876-913.
75. Drucker DJ. Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol 2003; 17: 161-171.
76. Egan JM, Bulotta A, Hui H, Perfetti R. GLP-1 receptor agonists are growth and differentiation factors for pancreatic islet beta cells. Diabetes Metab Res Rev 2003; 19: 115-123.
77. Shima K, Hirota M, Ohboshi C. Effect of glucagon-like peptide-1 on insulin secretion. Regul Pept 1988; 22: 245-252.
78. Matsuyama T, Komatsu R, Namba M, Watanabe N, Itoh H, Tarui S. Glucagon-like peptide-1 (7-36 amide): a potent glucagonostatic and insulinotropic hormone. Diabetes Res Clin Pract 1988; 5: 281-284.
79. Gutniak MK, Holst JJ, Ørskov C, Åhren B, Efendic S. Antidiabetogenic effect of glucagon-like peptide-1 (7-36) amide in normal subjects and patients with diabetes mellitus. N Engl J Med 1992; 326: 1316-1322.
80. Nauck MA, Kleine N, Ørskov C, Holst JJ, Willms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993; 36: 741-744.
81. Rachman J, Gribble FM, Barrow BA, Levy JC, Buchanan KD, Turner RC. Normalization of insulin responses to glucose by overnight infusion of glucagon-like peptide 1 (7-36) amide in patients with NIDDM. Diabetes 1996; 45: 1524-1530.
82. Rachman J, Gribble FM, Levy JC, Turner RC. Near-normalization of diurnal glucose concentrations by continuous administration of glucagon-like peptide 1 (GLP-1) in subjects with NIDDM. Diabetologia 1997; 40: 205-211.
83. Nauck MA, Sauerwald A, Ritzel R, Holst JJ, Schmiegel W. Influence of glucagon-like peptide 1 on fasting glycemia in type 2 diabetic patients treated with insulin after sulfonylurea failure. Diabetes Care 1998; 21: 1925-1931.
84. Meier JJ, Gallwitz B, Salmen S, et al. Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes. J Clin Endocrinol Metab 2003; 88: 2719-2725.
85. Holz GG, Kuhtreiber WM, Habener JF. Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1 (7-37). Nature 1993; 361: 362-365.
86. (2+)-signaling pathway in pancreatic beta-cells by the insulinotropic hormone glucagon-like peptide-1. J Biol Chem 1995; 270: 17 749-17 757.
87. Gromada J, Rorsman P, Dissing S, Wulff BS. Stimulation of cloned human glucagon-like peptide 1 receptor expressed in HEK 293 cells induces cAMP-dependent activation of calcium-induced calcium release. FEBS Lett 1995; 373: 182-186.
88. Gromada J, Dissing S, Bokvist K, et al. Glucagon-like peptide I increases cytoplasmic cacium in insulin-secreting βTC3-cells by enhancement of intracellular calcium mobilization. Diabetes 1995; 44: 767-774.
89. Gromada J, Ding WG, Barg S, Renstrom E, Rorsman P. Multisite regulation of insulin secretion by cAMP-increasing agonists: evidence that glucagon-like peptide 1 and glucagon act via distinct receptors. Pflugers Arch 1997; 434: 515-524.
90. Gromada J, Bokvist K, Ding WG, Holst JJ, Nielsen JH, Rorsman P. Glucagon-like peptide 1 (7-36) amide stimulates exocytosis in human pancreatic beta-cells by both proximal and distal regulatory steps in stimulus-secretion coupling. Diabetes 1998; 47: 57-65.
91. Gromada J, Holst JJ, Rorsman P. Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pflügers Arch - Eur J Physiol 1998; 435: 583-594.
92. 2+ channels of pancreatic B-cells through cAMP signaling. Jpn J Physiol 1997; 47(Suppl. 1): 13-14.
93. Nauck MA, Heimesaat MM, Behle K, et al. Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab 2002; 87: 1239-1246.
94. Hargrove DM, Nardone NA, Persson LM, et al. Comparison of the glucose dependency of glucagon-like peptide-1 (7-37) and glyburide in vitro and in vivo. Metabolism 1996; 45: 404-409.
95. Gerich JE Abnormal glucagon secretion in type 2 (noninsulin-dependent) diabetes mellitus: causes and consequences. In Diabetes Mellitus: Pathophysiology and Therapy, Creutzfeldt W. Lefèbvre P. (eds). Springer Verlag: Berlin, Heidelberg, 1989; 127-133.
96. Meier JJ, Gallwitz B, Siepmann N, Holst JJ, Deacon CF, Schmidt WE, Nauck MA. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia 46: 798-801, 2003.
97. Ørskov C, Holst JJ, Nielsen OV. Effect of truncated glucagon-like peptide-1 [proglucagon-(78-107) amide] on endocrine secretion from pig pancreas, antrum, and nonantral stomach. Endocrinology 1988; 123: 2009-2013.
98. Heller RS, Aponte GW. Intra-islet regulation of hormone secretion by glucagon-like peptide-1-(7-36) amide. Am J Physiol 1995; 269: G852-G860.
99. Wei Y, Mojsov S. Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett 1995; 358 219-224.
100. Wei Y, Mojsov S. Distribution of GLP-1 and PACAP receptors in human tissues. Acta Physiol Scand 1996; 157: 355-357.
101. Creutzfeldt WO, Kleine N, Willms B, Ørskov C, Holst JJ, Nauck MA. Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7-36) amide in type I diabetic patients. Diabetes Care 1996; 19: 580-586.
102. Gerich JE. Physiology of glucose homeostasis. Diabetes Obes Metab 2000; 2: 345-350.
103. Horowitz M, Edelbroek MA, Wishart JM, Straathof JW. Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia 1993; 36: 857-862.
104. Horowitz M, O'Donovan D, Jones KL, Feinle C, Rayner CK, Samsom M. Gastric emptying in diabetes: clinical significance and treatment. Diabetic Med 2002; 19: 177-194.
105. Wettergren A, Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ. Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 1993; 38: 665-673.
106. Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol (Endocrinol Metab) 1997; 273: E981-E988.
107. Willms B, Werner J, Holst JJ, Ørskov C, Creutzfeldt W, Nauck MA. Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients. J Clin Endocrinol Metab 1996; 81: 327-332.
108. Kjems LL, Holst JJ, Vølund A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 2003; 52: 380-386.
109. Schirra J, Houk P, Wank U, Arnold R, Goke B, Katschinski M. Effects of glucagon-like peptide-1 (7-36) amide on antropyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans. Gut 2000; 56: 622-631.
110. Schirra J, Wank U, Arnold R, Göke B, Katschinski M. Effects of glucagon-like peptide-1 (7-36) amide on motility and sensation of the proximal stomach in humans. Gut 2002; 50: 341-348.
111. Meier JJ, Gallwitz B, Nauck MA. Glucagon-like peptide 1 and Gastric Inhibitory Polypeptide: potential applications in type 2 diabetes mellitus. BioDrugs 2003; 17: 93-102.
112. Eissele R, Koop H, Arnold R. Effect of glucagon-like peptide-1 on gastric somatostatin and gastrin secretion in the rat. Scand J Gastroenterol 1990; 25: 449-454.
113. Schjoldager BT, Mortensen PE, Christiansen J, Ørskov C, Holst JJ. GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans. Dig Dis Sci 1989; 34: 703-708.
114. 2: a physiological inhibitor of gastric acid secretion in man. J Endocrinol 1990; 126: 169-173.
115. Wettergren A, Petersen H, Ørskov C, Christiansen J, Sheikh SP, Holst JJ. Glucagon-like peptide-1 (7-36) amide and peptide YY from the L-cell of the ileal mucosa are potent inhibitors of vagally induced gastric acid secretion in man. Scand J Gastroenterol 1994; 29 501-505.
116. Wettergren A, Maina P, Boesby S, Holst JJ. Glucagon-like peptide-1 (7-36) amide and peptide YY have additive inhibitory effect on gastric acid secretion in man. Scand J Gastroenterol 1997; 32 552-555.
117. Fung LC, Chisholm C, Greenberg GR. Glucagon-like peptide-1-(7-36) amide and peptide YY mediate intraduodenal fat-induced inhibition of acid secretion in dogs. Endocrinology 1998; 139 189-194.
118. Schirra J, Leicht P, Hildebrand P, et al. Mechanisms of the antidiabetic action of subcutaneous glucagon-like peptide-1 (7-36) amide in non-insulin dependent diabetes mellitus. J Endocrinol 1998; 156: 177-186.
119. Imeryuz N, Yegen BC, Bozkurt A, Coskun T, Villanueva Penacarrillo ML, Ulusoy NB. Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. Am J Physiol (Gastroenterol Liver) 1997; 273: G920-G927.
120. Wettergren A, Wojdemann M, Meisner S, Stadil F, Holst JJ. The inhibitory effect of glucagon-like peptide-1 (GLP-1) 7-36 amide on gastric acid secretion in humans depends on an intact vagal innervation. Gut 1997; 40: 597-601.
121. Schick RR, Zimmermann JP, vorm Walde T, Schusdziarra V, Classen M. Glucagon-like-peptide (GLP)-1-(7-36)-amide: a central suppressor of food intake in rats. Gastroenterology 1992; 102 Suppl. 1) A756.
122. Szayna M, Doyle ME, Betkey JA, et al. Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology 2000; 141: 1936-1941.
123. Larsen PJ, Fledelius C, Knudsen LB, Tang-Christensen M. Systemic administration of the long-acting GLP-1 analogue, NN2211, induces lasting and reversible weight loss in both normal and obese rats. Diabetes 2001; 50: 2530-2539.
124. Tang Christensen M, Larsen PJ, Göke R, et al. Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats. Am J Physiol (Regul Integr Comp) 1996; 271: R848-R856.
125. Scrocchi LA, Brown TJ, MaClusky N, et al. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med 1996; 2: 1254-1258.
126. Gutzwiller J-P, Drewe J, Göke B, et al. Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physiol (Regul Integr Comp) 1999; 276: R1541-R1544.
127. Meier JJ, Gallwitz B, Schmidt WE, Nauck MA. Glucagon-like peptide 1 (GLP-1) as a regulator of food intake and body weight: therapeutic perspectives. Eur J Pharmacol 2002; 440: 269-279.
128. Verdich C, Flint A, Gutzwiller JP, et al. A meta-analysis of the effects of glucagon-like peptide-1 (7-36) amide on ad libidum energy intake in humans. J Clin Endocrinol Metab 2001; 86: 4382-4389.
129. Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002; 359: 824-830.
130. Schick RR, Zimmermann JP, vorm Walde T, Schusdziarra V. Peptides that regulate food intake: glucagon-like peptide 1-(7-36) amide at lateral and medial hypothalamic sites to suppress feeding in rats. Am J Physiol (Integr Comp Physiol) 2003; 284: R1427-R1435.
131. Ørskov C, Poulsen SS, Møller M, Holst JJ. Glucagon-like peptide I receptors in the subfornical organ and the area postrema are accessible to circulating glucagon-like peptide I. Diabetes 1996; 45: 832-835.
132. During MJ, Cao L, Zuzga DS, et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Medicine 2003; 9: 1173-1179.
133. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003; 52: 102-110.
134. Ritzel RA, Butler PC. Replication increases beta-cell vulnerability to human islet amyloid polypeptide-induced apoptosis. Diabetes 2003; 52: 1701-1708.
135. Mandrup-Poulsen T. Beta-cell apoptosis: stimuli and signaling. Diabetes 2001; 50(Suppl. 1): 58-63.
136. Farilla L, Hui H, Bertolotto C, et al. Glucagon-like peptide-1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats. Endocrinology 2002; 143: 4397-4408.
137. Li Y, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ. Glucagon-like peptide-1 receptor signalling modulates beta cell apoptosis. J Biol Chem 2003; 278: 471-478.
138. Hui H, Nourparvar A, Zhao X, Perfetti R. Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5′-adenosine monophosphate-dependent protein kinase A- and a phosphatidylinositol 3-kinase-dependent pathway. Endocrinology 2003; 144: 1444-1455.
139. Xu G, Stoffers DA, Habener JF, Bonner-Weir S. Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased b-cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999; 48: 2270-2276.
140. Buteau J, Foisy S, Rhodes CJ, Carpenter L, Biden TJ, Prentki M. Protein kinase Czeta activation mediates glucagon-like peptide-1-induced pancreatic beta-cell proliferation. Diabetes 2001; 50: 2237-2243.
141. Perfetti R, Zhou J, Doyle ME, Egan JM. Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats. Endocrinology 2000; 141: 4600-4605.
142. Buteau J, Foisy S, Joly E, Prentki M. Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor. Diabetes 2003; 52: 124-132.
143. Abraham EJ, Leech CA, Lin JC, Zulewski H, Habener JF. Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells. Endocrinology 2002; 143: 3152-3161.
144. Tourrel C, Bailbe D, Meile MJ, Kergoat M, Portha B. Glucagon-like peptide-1 and exendin-4 stimulate beta-cell neogenesis in streptozotocin-treated newborn rats resulting in persistently improved glucose homeostasis at adult age. Diabetes 2001; 50: 1562-1570.
145. Tyrberg B, Ustinov J, Otonkoski T, Andersson A. Stimulated endocrine cell proliferation and differentiation in transplanted human pancreatic islets: effects of the ob gene and compensatory growth of the implantation organ. Diabetes 2001; 50: 301-307.
146. Buteau J, Roduit R, Susini S, Prentki M. Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) DNA binding activity in beta (INS-1)-cells. Diabetologia 1999; 42: 856-864.
147. Wang X, Cahill CM, Pineyro MA, Zhou J, Doyle ME, Egan JM. Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells. Endocrinology 1999; 140: 4904-4907.
148. Wang X, Zhou J, Doyle ME, Egan JM. Glucagon-like peptide-1 causes pancreatic duodenal homeobox-1 protein translocation from the cytoplasm to the nucleus of pancreatic beta-cells by a cyclic adenosine monophosphate/protein kinase A-dependent mechanism. Endocrinology 2001; 142: 1820-1827.
149. Rafiq I, da Silva Xavier G, Hooper S, Rutter GA. Glucose-stimulated preproinsulin gene expression and nuclear translocation of pancreatic duodenum homeobox-1 require activation of phosphatidylinositol 3-kinase but not p38 MAPK/SAPK2. J Biol Chem 2000; 275: 15 977-15 984.
150. Wang Y, Egan JM, Raygada M, Nadiv O, Roth J, Montrose Rafizadeh C. Glucagon-like peptide-1 affects gene transcription and messenger ribonucleic acid stability of components of the insulin secretory system in RIN 1046-38 cells. Endocrinology 1995; 136 4910-4917.
151. D'Alessio D, Kahn SE, Leusner CR, Ensinck JW. Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. J Clin Invest 1994; 93: 2263-2266.
152. Egan JM, Meneilly GS, Habener JF, Elahi D. Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state. J Clin Endocrinol Metab 2002; 87: 3768-3773.
153. Prigeon RL, Quddusi S, Paty B, D'Alessio DA. Suppression of endogenous glucose production by glucagon-like peptide 1 independent of islet hormones: an extrapancreatic effect of an incretin hormone. Am J Physiol (Endocrinol Metab) 2003; 285: E701-E707.
154. Vella A, Shah P, Basu R, Basu A, Holst JJ, Rizza RA. Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes. Diabetes 2000; 49 611-617.
155. Vella A, Shah P, Reed AS, Adkins AS, Basu R, Rizza RA. Lack of effect of exendin-4 and glucagon-like peptide-1-(7,36)-amide on insulin action in non-diabetic humans. Diabetologia 2002; 45: 1410-1415.
156. Vella A, Shaw P, Basu R, et al. Effect of glucagon-like peptide-1(7-36)-amide on initial splanchnic glucose uptake and insulin action in humans with type 1 diabetes. Diabetes 2001; 50: 565-572.
157. Meneilly GS, McIntosh CH, Pederson RA, et al. Effect of glucagon-like peptide 1 on non-insulin-mediated glucose uptake in the elderly patient with diabetes. Diabetes Care 2001; 24: 1951-1956.
158. Pospisilik JA, Stafford SG, Demuth HU, et al. Long-term treatment with dipeptidyl peptidase IV inhibitor improves hepatic and peripheral insulin sensitivity in the VDF Zucker rat: a euglycemic-hyperinsulinemic clamp study. Diabetes 2002; 51: 2677-2683.
159. Nishizawa M, Moore MC, Shiota M, et al. Effect of intraportal glucagon-like peptide-1 on glucose metabolism in conscious dogs. Am J Physiol (Endocrinol Metab) 2003; 284: E1027-E1036.
160. Dillon JS, Tanizawa Y, Wheeler MB, et al. Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor. Endocrinology 1993; 133: 1907-1910.
161. Ørskov L, Holst J, Moller J, et al. GLP-1 does not acutely affect insulin sensitivity in healthy man. Diabetologia 1996; 39: 552-556.
162. Åhren B, Larsson H, Holst JJ. Effects of glucagon-like peptide-1 on islet function and insulin sensitivity in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab
163. Stumvoll M, Tataranni PA, Stefan N, Vozarova B, Bogardus C. Glucose allostasis. Diabetes 2003; 52: 903-909.
164. Vilsboll T, Krarup T, Madsbad S, Holst JJ. Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept 2003; 114: 115-121.
165. Balkan B, Li X. Portal GLP-1 administration in rats augments the insulin response to glucose via neuronal mechanisms. Am J Physiol Regulatory Integrative Comp Physiol 2000; 279: R1449-R1454.
166. Burcelin R, Da Costa A, Drucker D, Thorens B. Glucose competence of the hepatoportal vein sensor requires the presence of an activated glucagon-like peptide-1 receptor. Diabetes 2001; 50 1720-1728.
167. Barragan JM, Rodriguez RE, Blazquez E. Changes in arterial blood pressure and heart rate induced by glucagon-like peptide-1-(7-36) amide in rats. Am J Physiol 1994; 266: E459-E466.
168. Barragan JM, Rodriguez RE, Eng J, Blazquez E. Interactions of exendin-(9-39) with the effects of glucagon-like peptide-1-(7-36) amide and of exendin-4 on arterial blood pressure and heart rate in rats. Regul Pept 1996; 67: 63-68.
169. Yamamoto H, Lee CE, Marcus JN, et al. Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. J Clin Invest 2002; 110: 43-52.
170. Barragan JM, Eng J, Rodriguez R, Blazquez E. Neural contribution to the effect of glucagon-like peptide-1-(7-36) amide on arterial blood pressure in rats. Am J Physiol (Endocrinol Metab) 1999; 277: E784-E791.
171. Gros R, You X, Baggio LL, et al. Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology 2003; 144: 2242-2252.
172. Beak SA, Small CJ, Ilovaiskaia I, et al. Glucagon-like peptide-1 (GLP-1) releases thyrotropin (TSH): characterization of binding sites for GLP-1 on alpha-TSH cells. Endocrinology 1996; 137: 4130-4138.
173. Beak SA, Heath MM, Small CJ, et al. Glucagon-like peptide-1 stimulates luteinizing hormone-releasing hormone secretion in a rodent hypothalamic neuronal cell line. J Clin Invest 1998; 101 1334-1341.
174. Creutzfeldt W, Ebert R. New developments in the incretin concept. Diabetologia 1985; 28: 565-573.
175. Perley MJ, Kipnis DM. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 1967; 46: 1954-1962.
176. Nauck M, Stöckmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 1986; 29: 46-54.
177. Brown JC. Gastric Inhibitory Polypeptide. Springer-Verlag: Heidelberg, 1982.
178. Pederson RA, Schubert HE, Brown JC. Gastric inhibitory polypeptide. Its physiologic release and insulinotropic action in the dog. Diabetes 24: 1050-1056, 1975.
179. Krarup T, Saurbrey N, Moody AJ, Kühl C, Madsbad S. Effect of porcine gastric inhibitory polypeptide on β-cell function in type I and type II diabetes mellitus. Metabolism 1988; 36: 677-682.
180. Krarup T. Immunoreactive gastric inhibitory polypeptide. Endocrine Reviews 1988; 9: 122-133.
181. Miyawaki K, Yamada Y, Yano H, et al. Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice. Proc Natl Acad Sci USA 1999; 96: 14 843-14 847.
182. Meier JJ, Hücking K, Holst JJ, Deacon C, Schmiegel W, Nauck MA. Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes 2001; 50: 2497-2504.
183. Ebert R, Creutzfeldt W. Influence of gastric inhibitory polypeptide antiserum on glucose-induced insulin secretion in rats. Endocrinol 1982; 111: 1601-1606.
184. Ebert R, Unger H, Creutzfeldt W. Preservation of incretin activity after removal of gastric inhibitory polypeptide (GIP) from rat gut extracts by immunoadsorption. Diabetologia 1983; 24: 449-454.
185. Qualmann C, Nauck MA, Holst JJ, Ørskov C, Creutzfeldt W. Insulinotropic actions of intravenous glucagon-like peptide-1 (GLP-1) [7-36 amide] in the fasting state in healthy subjects. Acta Diabetol 1995; 32: 13-16.
186. Wang Z, Wang RM, Owji AA, Smith DM, Ghatei MA, Bloom SR. Glucagon-like peptide-1 is a physiological incretin in rat. J Clin Invest 1995; 95: 417-421.
187. Kolligs F, Fehmann HC, Göke R, Göke B. Reduction of the incretin effect in rats by the glucagon-like peptide 1 receptor antagonist exendin (9-39) amide. Diabetes 1995; 44: 16-19.
188. D'Alessio D, Vogel R, Prigeon R, et al. Elimination of the action of glucagon-like peptide 1 causes an impairment of glucose tolerance after nutrient ingestion by healthy baboons. J Clin Invest 1996; 97: 133-138.
189. Gault VA, O'Harte FP, Harriot P, Mooney MH, Green BD, Flatt PR. Effects of the novel (Pro(3))GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin. Diabetologia 2003; 46: 222-230.
190. Nauck MA. Is glucagon-like peptide 1 an incretin hormone? Diabetologia 1999; 42: 373-379.
191. Grossman MI. Candidate hormones of the gut. 13. Enterogastrone. Gastroenterology 1974; 67: 745-746.
192. Ebert R, Creutzfeldt W. Gastric inhibitory polypeptide. Clin Gastroenterol 1980; 9: 679-698.
193. Li P, Chang TM, Chey WY. Secretin inhibits gastric acid secretion via a vagal afferent pathway in rats. Am J Physiol (Gastrointest Liver Physiol) 1998; 275: G22-G28.
194. Wojdemann M, Wettergren A, Hartmann B, Hilsted L, Holst JJ. Inhibition of sham feeding-stimulated human gastric acid secretion by glucagon-like peptide-2. J Clin Endocrinol Metab 1999; 84: 2513-2517.
195. Pappas TN, Debas HT, Taylor IL. Enterogastrone-like effect of peptide YY is vagally mediated in the dog. J Clin Invest 1986; 77: 49-53.
196. Göke R, Fehmann H-C, Göke B. Glucagon-like peptide-1 (7-36) amide is a new incretin/enterogastrone candidate. Eur J Clin Invest 1991; 21: 135-144.
197. Hansen AB, Gespach CP, Rosselin GE, Holst JJ. Effect of truncated glucagon-like peptide 1 on cAMP in rat gastric glands and HGT-1 human gastric cancer cells. FEBS Lett 1988; 236: 119-122.
198. Uttenthal LO, Blazquez E. Characterization of high-affinity receptors for truncated glucagon-like peptide-1 in rat gastric glands. FEBS Lett 1990; 262: 139-141.
199. Layer P, Holst JJ, Grandt D, Goebell H. Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans. Dig Dis Sci 1995; 40: 1074-1082.
200. Gutzwiller J-P, Göke B, Drewe J, et al. Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut 1999; 44: 81-86.
201. Gutzwiller JP, Göke B, Drewe J, et al. Glucagon-like peptide-1 is a physiologic regulator of food intake in humans. Gastroenterol 1997; 112(Suppl. A): 1153.
202. Donahey JCK, van Dijk G, Woods SC, Seeley RJ. Intraventricular GLP-1 reduces short- but not long-term food intake or body weight in lean and obese rats. Brain Res 1998; 229: 75-83.
203. Stoffers DA, Kiefer TJ, Hussain MA, et al. Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. Diabetes 2000; 49: 741-748.
204. De Leon DD, Deng S, Madani R, Ahima RS, Drucker DJ, Stoffers DA. Role of endogenous glucagon-like peptide-1 in islet regeneration after partial pancreatectomy. Diabetes 2003; 52: 365-371.
205. Ling Z, Wu D, Zambre Y, et al. Glucagon-like peptide 1 receptor signalling influences topography of islet cells in mice. Virchows Arch 2001; 438: 382-387.
206. Ørskov C, Jeppesen J, Madsbad S, Holst JJ. Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine. J Clin Invest 1991; 87: 415-423.
207. Toft-Nielsen MB, Damholt MB, Madsbad S, et al. Determinants of impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001; 86: 3717-3723.
208. Vilsbøll T, Agersø H, Krarup T, Holst JJ. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab 2003; 88 220-224.
209. Ruiz-Grande C, Alarcón C, Alcántara A, et al. Renal catabolism of truncated glucagon-like peptide 1. Horm Metab Res 1993; 25: 612-616.
210. Groop LC, Pelkonen R, Koskimies S, Bottazzo GF, Doniach D. Secondary failure to treatment with oral antidiabetic agents in non-insulin-dependent diabetes. Diabetes Care 1986; 9: 129-133.
211. Vilsbøll T, Krarup T, Madsbad S, Holst JJ. Defective amplification of the late phase insulin response to glucose by GIP in obese type II diabetic patients. Diabetologia 2002; 45: 1111-1119.
212. Vilsbøll T, Toft-Nielsen MB, Krarup T, Madsbad S, Dinesen B, Holst JJ. Evaluation of beta-cell secretory capacity using glucagon-like peptide 1. Diabetes Care 2000; 23: 807-812.
213. Nauck MA, Holst JJ, Willms B. Glucagon-like peptide 1 and its potential in the treatment of non-insulin-dependent diabetes mellitus. Horm Metab Res 1997; 29: 411-416.
214. Toft-Nielsen MB, Madsbad S, Holst JJ. Determinants of the effectiveness of glucagon-like peptide-1 in type 2 diabetes. J Clin Endocrinol Metab 2001; 86: 3853-3860.
215. Larsen J, Hylleberg B, Ng K, Damsbo P. Glucagon-like peptide-1 infusion must be maintained for 24 h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment. Diabetes Care 2001; 24: 1416-1421.
216. Toft-Nielsen M-B, Madsbad S, Holst JJ. Continuous subcutaneous infusion of Glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients. Diabetes Care 1999; 22: 1137-1143.
217. Fineman MS, Bicsak TA, Shen LZ, et al. Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care 2003; 26: 2370-2377.
218. Juhl CB, Hollingdal M, Sturis J, et al. Bedtime administration of NN2211, a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes. Diabetes 2002; 51: 424-429.
219. Meier JJ, Nauck MA, Schmidt WE, Gallwitz B. Gastric inhibitory polypeptide (GIP): the neglected incretin revisited. Regul Peptides 2002; 107: 1-13.
220. Elahi D, McAloon Dyke M, Fukagawa NK, et al. The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects. Regul Pept 1994; 51: 63-74.
221. Holst JJ, Gromada J, Nauck MA. The pathogenesis of NIDDM involves a defective expression of the GIP receptor. Diabetologia 1997; 40: 984-986.
222. Deacon CF, Nauck MA, Meier JJ, Hücking K, Holst JJ. Degradation of endogenous and exogenous gastric inhibitory polypeptide (GIP) in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide. J Clin Endocrinol Metab 2000; 85 3575-3581.
223. Ding W-G, Gromada J. Protein kinase A-dependent stimulation of exocytosis in mouse pancreatic β-cells by glucose-dependent insulinotropic polypeptide. Diabetes 1997; 46: 615-621.
224. Kubota A, Yamada Y, Hayami T, et al. Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects. Diabetes 1996; 45: 1701-1705.
225. Amlind K, Ambye L, Urhammer SA, et al. Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell response and functional expression studies in Chinese hamster fibroblast cells. Diabetologia 1998; 41: 1194-1198.
226. Lynn PC, Pamir N, Ng EH, McIntosh CH, Kieffer' TJ, Pederson RA. Defective glucose-dependent insulinotropic polypeptide receptor expression in diabetic fatty Zucker rats. Diabetes 2001; 50: 1004-1011.
227. Wolfe MM, Boylan MO, Kiefer TJ, Tseng C-C. Glucose-dependent insulinotropic polypeptide (GIP). In Gastrointestinal Endocrinology (1st edn), Greenley GH. (ed). Humana Press Inc.: Totowa, 1998; 439-466.
228. Tseng CC, Boylan MO, Jarboe LA, Usdin TB, Wolfe MM. Chronic desensitization of the glucose-dependent insulinotropic polypeptide receptor in diabetic rats. Am J Physiol (Endocrinol Metab) 1996; 270: E661-E666.
229. Tseng C-C, Zhang X-Y. The cysteine of the cytoplasmatic tail of glucose-dependent insulinotropic peptide receptor mediates its chronic desensitisation and down-regulation. Moll Cell Endocrinol 1998; 139: 179-186.
230. Vaag AA, Holst JJ, Volund A, Beck-Nielsen H. Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM) - evidence for decreased glucagon-like peptide-1 secretion during oral glucose ingestion in NIDDM twins. Eur J Endocrinol 1996; 135: 435-432.
231. Meier JJ, Nauck MA, Siepmann N, et al. Similar insulin secretory response to a GIP bolus injection at euglycemia in first-degree relatives of patients with type 2 diabetes and control subjects. Metabolism 2003; 52: 1579-1585.
232. Nauck MA, El-Ouaghlidi A, Gabrys B, et al. Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with type 2 diabetes. Regul Peptides 2004; 122: 209-217.
233. Dupré J, Caissignac Y, McDonald TJ, Van Vliet S. Stimulation of glucagon secretion by gastric inhibitory polypeptide in patients with hepatic cirrhosis and hyperglucagonemia. J Clin Endocrinol Metab 1991; 72: 125-129.
234. Wolfe MM, Reel GM. Inhibition of gastrin release by gastric inhibitory peptide mediated by somatostatin. Am J Physiol (Gastrointest Liver Physiol) 1986; 250: G331-G335.
235. Yamagishi T, Debas HT. Gastric inhibitory polypeptide (GIP) is not the primary mediator of the enterogastrone action of fat in the dog. Gastroenterology 1980; 78: 931-936.
236. Nauck MA, Bartels E, Ørskov C, Ebert R, Creutzfeldt W. Lack of effect of synthetic human gastric inhibitory polypeptide and glucagon-like peptide 1 [7-36 amide] infused at near physiological concentrations on pentagastrin-stimulated gastric acid secretion in normal human subjects. Digestion 1992; 52: 214-221.
237. Meier JJ, Goetze O, Anstipp J, et al. Gastric inhibitory polypeptide does not inhibit gastric emptying in humans. Am J Physiol (Endocrinol Metab) 2004; 286: E621-625.
238. Usdin TB, Mesey E, Button DC, Brownstein MJ, Booner TI. Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain. Endocrinology 1993; 133: 2861-2870.
239. Trümper A, Trümper K, Trusheim H, Arnold R, Göke B, Horsch D. Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1) cells by pleiotropic signaling. Mol Endocrinol 2001; 15: 1559-1570.
240. Trümper A, Trümper K, Horsch D. Mechanisms of mitogenic and anti-apoptotic signalling by glucose-dependent insulinotropic polypeptide in beta(INS-1)-cells. J Endocrinol 2002; 174: 233-246.
241. Krarup T, Madsbad S, Moody A, et al. Diminished immunoreactive gastric inhibitory polypeptide response to a meal in newly diagnosed type I diabetics. J Clin Endocrinol Metab 1983; 56: 1306-1312.
242. Krarup T, Madsbad S, Moody AJ. Immunoreactive gastric inhibitory polypeptide response to a meal during the first eighteen months after diagnosis of type 1 (insulin dependent) diabetes mellitus. J Clin Endocrinol Metab 1985; 60: 120-125.
243. Dupré J, Behme MT, Hramiak M, et al. Glucagon-like peptide 1∼reduces postprandial glycemic excursions in IDDM. Diabetes 1995; 44: 626-630.
244. Dupré J, Behme MT, Hramiak M, McDonald TJ. Subcutaneous glucagon-like peptide I combined with insulin normalizes postcibal glycemic excursions in IDDM. Diabetes Care 1997; 20: 381-384.
245. Behme MT, Dupre J, McDonald TJ. Glucagon-like peptide 1 improved glycemic control in type 1 diabetes. BMC Endocr Disord 2003; 3: 3.
246. Fukase N, Igarashi M, Takahashi H, et al. Hypersecretion of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide in obese patients. Diabetic Med 1993; 10 44-49.
247. Vilsbøll T, Krarup T, Sonne J, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 2003; 88: 2706-2713.
248. Tomasik PJ, Sztefko K, Malek A. GLP-1 as a satiety factor in children with eating disorder. Horm Metab Res 2002; 34: 77-80.
249. Scrocchi L, Hill ME, Saleh J, Perkins B, Drucker DJ. Elimination of glucagon-like peptide 1R signalling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action. Diabetes 2000; 49: 1552-1560.
250. Miyawaki K, Yamada Y, Ban N, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 2002; 8: 738-742.
251. Brun JF, Fedou C, Mercier J. Postprandial reactive hypoglycemia. Diabetes Metab 2000; 26: 337-351.
252. Roth DA, Maede RC. Hyperinsulinism-hypoglycemia in the postgastrectomy patient. Diabetes 1965; 14: 526-528.
253. Andreasen JJ, Ørskov C, Holst JJ. Secretion of glucagon-like peptide-1 and reactive hypoglycemia after partial gastrectomy. Digestion 1994; 55: 221-228.
254. Gebhard B, Holst JJ, Biegelmayer C, Miholic J. Postprandial GLP-1, norepinephrine, and reactive hypoglycemia in dumping syndrome. Dig Dis Sci 2001; 46: 1915-1923.
255. Toft-Nielsen M, Madsbad S, Holst JJ. Exaggerated secretion of glucagon-like peptide-1 (GLP-1) could cause reactive hypoglycemia. Diabetologia 1998; 41: 1180-1186.
256. Vilsbøll T, Krarup T, Madsbad S, Holst JJ. No reactive hypoglycaemia in type 2 diabetic patients after subcutaneous administration of GLP-1 and intravenous glucose. Diabetes Care 2001; 18: 144-149.
257. Knop FK, Vilsboll T, Larsen S, Madsbad S, Holst JJ, Krarup T. No reactive hypoglycemia after subcutaneous administration of glucagon-like peptide-1 in lean type 2 diabetic patients and in patients with diabetes secondary to chronic pancreatitis. Diabetes Care 2003; 26: 2581-2587.
258. Todd JF, Stanley SA, Roufosse CA, et al. A tumour that secretes glucagon-like peptide-1 and somatostatin in a patient with reactive hypoglycemia and diabetes. Lancet 2003; 361: 228-230.
259. Byrne MM, McGregor GP, Barth P, Rothmund M, Göke B, Arnold R. Intestinal proliferation and delayed intestinal transit in a patient with a GLP-1-, GLP-2- and PYY-producing neuroendocrine carcinoma. Digestion 2001; 63: 61-68.
260. Holst JJ. Glucagon-like peptide 1 (GLP-1): an intestinal hormone, signalling nutritional abundance, with an unusual therapeutic potential. Trends Endocrinol Metab 1999; 10: 229-235.
261. Polonsky KS, Given BD, Hirsch LJ, et al. Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med 1988; 318: 1231-1239.
262. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 1999; 104: 787-794.
263. Pratley RE, Weyer C. The role of impaired early insulin secretion in the pathogenesis of type II diabetes mellitus. Diabetologia 2001; 44: 929-945.
264. Schmitz O, Pørksen N, Nyholm B, et al. Disorderly and nonstationary insulin secretion in relatives of patients with NIDDM. Am J Physiol (Endocrinol Metab) 1997; 272: E218-E226.
265. Quddusi S, Vahl TP, Hanson K, Prigeon RL, D'Alessio DA. Differential effects of acute and extended infusions of glucagon-like peptide-1 on first- and second-phase insulin secretion in diabetic and nondiabetic humans. Diabetes Care 2003; 26: 791-798.
266. Pørksen N, Grofte B, Nyholm B, et al. Glucagon-like peptide 1 increases mass but not frequency or orderliness of pulsatile insulin secretion. Diabetes 1998; 47: 45-49.
267. Ritzel R, Schulte M, Porksen N, et al. Glucagon-like peptide 1 increases secretory burst mass of pulsatile insulin secretion in patients with type 2 diabetes and impaired glucose tolerance. Diabetes 2001; 50: 776-784.
268. Baron AD, Schaeffer L, Shragg P, Kolterman OG. Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type 2 diabetics. Diabetes 1987; 36: 274-283.
269. Horowitz M, Harding PE, Maddox AF, et al. Gastric and oesophageal emptying in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1989; 32: 151-159.
270. Horowitz M, Fraser R. Disordered gastric motor function in diabetes mellitus. Diabetologia 1994; 37: 543-551.
271. Scott LJ, Spencer CM. Miglitol: a review of its therapeutic potential in type 2 diabetes mellitus. Drugs 2000; 59: 521-549.
272. Hu FB, Manson JE, Stampfer MJ, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. New Engl J Med 2001; 345: 790-797.
273. Hui H, Wright C, Perfetti R. Glucagon-like peptide 1 induces differentiation of islet duodenal homeobox-1 positive pancreatic ductal cells into insulin-secreting cells. Diabetes 2001; 50: 785-796.
274. Sinha R, Fisch G, Teague B, et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 2002; 346: 802-810.
275. Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptide YY 3-36. N Engl J Med 2003; 349: 941-948.
276. Heise T, Heinemann L, Starke AA. Simulated postaggression metabolism in healthy subjects: metabolic changes and insulin resistance. Metabolism 1998; 47: 1263-1268.
277. Mizock BA. Alterations in carbohydrate metabolism during stress: a review of the literature. Am J Med 1995; 98: 75-84.
278. Nauck MA, Deifuß S, Klamann A, Sarfert P, Schmiegel W. Influence of glycemic control on size of myocardial infarction and long-term survival of type 2 diabetic patients (abstract). Diabetes Res Clin Plact 2000; 50(Suppl. 1): 300-301.
279. Malmberg K, Ryden L, Hamsten A, Herlitz J, Waldenström A, Wedel H. Mortality prediction in diabetic patients with myocardial infarction: experiences from the DIGAMI study. Cardiovasc Res 1997; 34: 248-253.
280. Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000; 355: 773-778.
281. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 2001; 32: 2426-2432.
282. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345: 1359-1367.
283. Malmberg K. Prospective randomised study of intensive treatment on long term survival after myocardial infarction in patients with diabetes mellitus: DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. Brit Med J 1997; 314: 1512-1515.
284. Meier JJ, Weyhe D, Michaely M, et al. Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes. Crit Care Med 2004; 32: 848-851.
285. Nauck MA, Walberg J, Vethacke A, Holst JJ, Senkal M, Gallwitz B. Reduction of hyperglycemia by intravenous GLP-1 in patients under parenteral nutrition (abstract). Diabetologia 2002; 45(Suppl. 2): A672.
286. Ritzel R, Ørskov C, Holst JJ, Nauck MA. Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP-1 [7-36 amide] after subcutaneous injection in healthy volunteers. Dose-response-relationships. Diabetologia 1995; 38: 720-725.
287. Deacon CF, Highes TE, Holst JJ. Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig. Diabetes 1998; 47: 764-769.
288. Deacon C, Danielsen P, Klarskov L, Olesen M, Holst JJ. Dipeptidyl peptidase IV inhibition reduces the degradation and clearance of GIP and potentiates its insulinotropic effects in anesthetized pigs. Diabetes 2001; 50: 1588-1597.
289. Pederson RA, White HA, Schlenzig D, Pauly RP, McIntosh CH, Demuth HU. Improved glucose tolerance in Zucker fatty rats by oral administration of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidine. Diabetes 1998; 47: 1253-1258.
290. Balkan B, Kwasnik L, Miserendino R, Holst JJ, Li X. Inhibition of dipeptidyl peptidase IV with NVP-DPP728 increases plasma GLP-1 (7-36 amide) concentrations and improves oral glucose tolerance in obese Zucker rats. Diabetologia 1999; 42: 1324-1331.
291. Åhren B, Holst JJ, Martensson H, Balkan B. Improved glucose tolerance and insulin secretion by inhibition of dipeptidyl peptidase IV in mice. Eur J Pharmacol 2000; 404: 239-245.
292. Deacon CF, Wamberg S, Bie P, Hughes TE, Holst JJ. Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV suppresses meal-induced incretin secretion in dogs. J Endocrinol 2002; 172: 355-362.
293. Sudre B, Broqua P, White RB, et al. Chronic inhibition of circulating dipeptidyl peptidase IV by FE 999 011 delays the occurrence of diabetes in male zucker diabetic fatty rats. Diabetes 2002; 51: 1461-1469.
294. Pospisilik JA, Stafford SG, Demuth HU, et al. Long-term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and beta-cell glucose responsiveness in VDF (fa/fa) Zucker rats. Diabetes 2002; 51: 943-950.
295. Åhren B, Simonsson E, Larsson H, et al. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care 2002; 25: 869-875.
296. Gorrell MD, Gysbers V, McCaughan GW. CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scand J Immunol 2001; 54: 249-264.
297. Kapitza C, Trautmann ME, Heise T, Heinemann L, Patterson B. Daily administration of LY307 161SR (GLP-1 analog) normalizes blood glucose in type 2 diabetes (abstract). Diabetes 2002; 51 Suppl. 2): A84.
298. Trautmann ME, Kapitza C, Mace KF, Patterson B, Hompesch M, Heise T. LY307 161 SR, a sustained release formulation of a GLP-1 analog, is suitable for once daily administration in patients with type 2 diabetes (abstract). Diabetes 2002; 51(Suppl. 1): A135.
299. Trautmann M, Chen C-F, Chappell J, et al. LY307 161 SR, a long-acting GLP-1 analog, improved glycemic control in patients with type 2 diabetes (abstract). Diabetes 2003; 52(Suppl. 1): A136.
300. Agersø H, Jensen LB, Elbrønd B, Rolan P, Zdravkovic M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 2002; 45: 195-202.
301. Elbrønd B, Jakobsen G, Larsen S, et al. Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose of NN2211, a long-acting glucagon-like peptide 1 derivative, in healthy male subjects. Diabetes Care 2002; 25: 1398-1404.
302. Chang AM, Jakobsen G, Sturis J, et al. The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes 2003; 52: 1786-1791.
303. Kim J-G, Baggio LL, Drucker DJ. The GLP-1-DAC analogue CJC-1131 upregulates insulin gene expression and exerts a memory effect on glycemic control in db/db mice (abstract). Diabetes 2002; 51 Suppl. 2): A340.
304. Lawrence B, Dreyfus JF, Wen S, Guivarch P-H, Drucker DJ, Castaigne J-P. CJC-1131, a long-acting GLP-1 derivative, exhibits an extended pharmacokinetik profile in healthy human volunteers (abstract). Diabetes 2003; 52(Suppl. 1): A125.
305. Eng J, Kleinman WA, Singh G, Raufman JP. Isolation and characterisation of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom: further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem 1992; 267: 7402-7405.
306. Göke R, Fehmann HC, Linn T, et al. Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. J Biol Chem 1993; 268: 19 650-19 655.
307. Chen YE, Drucker DJ. Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem 1997; 272: 4108-4115.
308. Greig NH, Holloway HW, De Ore KA, et al. Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations. Diabetologia 1999; 42 45-50.
309. Young AA, Gedulin BR, Bhavsar S, et al. Glucose lowering and insulin-sensitizing actions of exendin-4. Diabetes 1999; 48: 1026-1034.
310. Edwards CM, Stanley SA, Davis R, et al. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol (Endocrinol Metab) 2001; 281 E155-E161.
311. Kolterman OG, Buse JB, Fineman MS, et al. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 2003; 88: 3082-3089.
312. Holst JJ. Enteroglucagon. Ann Rev Physiol 1997; 59 257-271.
313. Ørskov C, Bersani M, Johnsen AH, Hojrup P, Holst JJ. Complete sequences of glucagon-like peptide-1 from human and pig small intestine. J Biol Chem 1989; 264: 12 826-12 829.
314. Cleator IG, Gourlay RH. Release of immunoreactive gastric inhibitory polypeptide (IR-GIP) by oral ingestion of food substances. Am J Surg 1975; 130: 128-135.
315. Wasada T, McCorkle K, Harris V, Kawai K, Howard B, Unger RH. Effect of gastric inhibitory polypeptide on plasma levels of chylomicron triglycerides in dogs. J Clin Invest 1981; 68: 1107-1110.
316. Eckel RH, Fujimoto WY, Brunzell JD. Gastric inhibitory polypeptide enhance lipoprotein lipase activity in cultured preadipocytes. Diabetes 1979; 28: 1141-1142.
317. Pamir N, Lynn FC, Buchan AM, et al. Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis. Am J Physiol (Endocrinol Metab) 2003; 284: E931-E939.
318. Willms B, Idowu K, Holst JJ, Creutzfeldt W, Nauck MA. Overnight GLP-1 normalizes fasting but not daytime plasma glucose values in NIDDM patients. Exptl Clin Endocrinol Diabetes 1998; 106: 103-107.
319. Nauck MA, Weber I, Bach I, et al. Normalization of fasting glycaemia by intravenous GLP-1 ([7-36 amide] or [7-37]) in type 2 diabetic patients. Diabetic Med 1998; 15: 937-945.
320. Nauck MA, Wollschläger D, Werner J, et al. Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7-36 amide]) in patients with NIDDM. Diabetologia 1996; 39: 1546-1553.